Summary of the invention
The object of the invention is to provide a kind of lentinan granule.This granule taking convenience can directly be swallowed, and also can pour drink-service in water, can be used as again feed additive and uses; Can reduce the stress that animal body produces due to administration, medicament contg is stable simultaneously, is adapted at veterinary clinic field application.
Another purpose of the present invention is to provide the preparation method of above-mentioned lentinan granule.
The present invention goes back the purposes that a purpose is to provide above-mentioned lentinan granule.
Realize that technical scheme of the present invention is as follows:
A kind of lentinan granule of the present invention, its raw material constituent and percentage by weight thereof are: lentinan 0.5~5%, filler 60~80%, binding agent 10~30%, water 0.5~5%.
The percentage by weight of the filler described in above-mentioned lentinan granule is preferably 70~80%.
The percentage by weight of the binding agent described in above-mentioned lentinan granule is preferably 15~30%.
The percentage by weight of the water described in above-mentioned lentinan granule is preferably 1~5%.
Filler described in above-mentioned lentinan granule is one or more the mixture in the filleies such as Icing Sugar, lactose, mannitol, sorbitol, starch, pregelatinized Starch (amylum pregelatinisatum), microcrystalline Cellulose or inorganic salt; Be preferably Icing Sugar.
Binding agent described in above-mentioned lentinan granule is one or more the mixture in syrup, PVP K30, rubber cement, dextrin, hydroxypropyl methylcellulose or methylcellulose; Be preferably PVP K30.
The material compositions such as above-mentioned lentinan, filler and binding agent all can obtain by open purchase on market.
The preparation method of above-mentioned lentinan granule comprises the steps:
(1), with lentinan, filler, binding agent philosophy drying, pulverizing; Lentinan is crossed 100 mesh sieves, and it is standby that filler, binding agent are crossed 80 mesh sieves;
(2), proportionally lentinan, filler after sieving are placed in mixer, more proportionally add gradually binding agent and water, mixing soft material, soft material do wet degree take " hold can agglomerating and tack-free, split with the light finger pressure energy " as spending;
(3), soft material crossed 16 mesh sieves make wet granular, then after 40 ℃ of air blast oven dry, with 20 order granulate, namely get the lentinan granule.
The application of above-mentioned lentinan granule on preparation medicament for immunity enhancement for animals.
The using method of the fragrant granule of above-mentioned lentinan, mixed feeding or mixed drink.
Compared with prior art, the present invention has advantages of: (1) lentinan granule of the present invention is easy to use, can directly swallow, and also can pour drink-service in water, also can be used as feed additive and uses; (2) lentinan granule of the present invention can reduce animal body due to the stress that administration produces, and more meets the animal welfare method; (3) dustability of lentinan granule of the present invention, tack, agglomeration, hygroscopicity etc. are all less, and medicament contg is stable.
The specific embodiment:
The present invention is described in detail by the following examples, but the present invention is not consisted of any restriction.
The preparation of embodiment 1 lentinan granule
Be prepared as follows:
(1), with lentinan (available from Meifeng Pharmaceutical Factory Fuzhou City of Jinting Pharmaceutical Co., Ltd., specification is 10g/ bottle (plastic bottle), authentication code is the accurate word Z1092011 of traditional Chinese medicines, as follows), Icing Sugar is (available from Shandong auspicious sign pharmaceutcal corporation, Ltd, specification is the 25kg/ bag, authentication code is the accurate word H20013420 of traditional Chinese medicines, as follows), hydroxypropyl methylcellulose is (available from Anhui Shanhe Medical Accessary Material Co., Ltd., specification is the 25kg/ bag, authentication code is No. the F0003rd, the accurate word (2002) of Anhui medicine) the philosophy drying, pulverize; Lentinan is crossed 100 mesh sieves, and it is standby that Icing Sugar, hydroxypropyl methylcellulose are crossed 80 mesh sieves.
(2), lentinan 50g, Icing Sugar 600g are placed in mixer, then add gradually hydroxypropyl methylcellulose 300g, water 50g, mixing is made soft material; Soft material is crossed 16 mesh sieves make wet granular, after then 40 ℃ of air blast are dried, with 20 order granulate, namely get the lentinan granule.
The preparation of embodiment 2 lentinan granules
Be prepared as follows:
(1), with lentinan, mannitol (available from Jiangsu Huanghai Sea pharmaceutcal corporation, Ltd, specification is the 25kg/ bag, authentication code is the accurate word H32022586 of traditional Chinese medicines), dextrin is (available from Anhui Shanhe Medical Accessary Material Co., Ltd., specification is the 25kg/ bag, authentication code is No. the F0001st, the accurate word (2002) of Anhui medicine) the philosophy drying, pulverize; Lentinan is crossed 100 mesh sieves, and it is standby that mannitol, dextrin are crossed 80 mesh sieves;
(2), lentinan 30g, mannitol 750g are placed in mixer, add gradually dextrin 200g and water 20g, mixing is made soft material; Soft material is crossed 16 mesh sieves make wet granular, after then 40 ℃ of air blast are dried, namely get the lentinan granule with 20 order granulate.
The preparation of embodiment 3 lentinan granules
Be prepared as follows:
(1), with lentinan, Icing Sugar, PVP K30 (available from Zhejiang Mao Yuan pharmaceutcal corporation, Ltd, specification is the 25kg/ bucket, and authentication code is asked the accurate word (2004) of Zhejiang medicine No. 224602, and is as follows) philosophy drying, pulverizing; Lentinan is crossed 100 mesh sieves, and it is standby that Icing Sugar, PVP K30 are crossed 80 mesh sieves;
(2), lentinan 50g, Icing Sugar 700g are placed in mixer, add gradually PVP K30 200g, water 50g, mixing is made soft material; Soft material is crossed 16 mesh sieves make wet granular, after then 40 ℃ of air blast are dried, namely get the lentinan granule with 20 order granulate.
The preparation of embodiment 4 lentinan granules
Be prepared as follows:
(1), with lentinan, microcrystalline Cellulose (available from the new large Fine Chemical Co., Ltd in Shandong, specification is the 20kg/ bag, and authentication code is No. the 208003rd, medicine Huaihe River, Shandong word (2005)), PVP K30 philosophy drying, pulverizing; Lentinan is crossed 100 mesh sieves, and it is standby that microcrystalline Cellulose, PVP K30 are crossed 80 mesh sieves;
(2), lentinan 5g, microcrystalline Cellulose 800g are placed in mixer, add gradually PVP K30 190g, water 5g, mixing is made soft material; Soft material is crossed 16 mesh sieves make wet granular, after then 40 ℃ of air blast are dried, with 20 order granulate, carry out granule packaging with medicinal composite membrane, namely get the lentinan granule.
The comparative efficacy test of embodiment 5 lentinan granules
Carry out as follows:
1 materials and methods
1.1 material
1.1.1 trial drug
The lentinan granule of embodiment 1, embodiment 2, embodiment 3, embodiment 4 preparations.
1.1.2 control drug
Lentinan film (control drug): specification is 10mg * 10 slice/plate/box, and authentication code is the accurate word H32026176 of traditional Chinese medicines, available from the Changjiang river, Jiangsu pharmaceutcal corporation, Ltd.
1.1.3 other drug and reagent
Vaccine: the weak malicious Seedling of new Zhi Erlian, the weak malicious Seedling of newcastle (ND-IV), new Zhi Erlian oil seepage, newcastle disease HI (ND-HI) test antigen are provided by Microbiological Lab of animal medicine institute of Agricultural University Of Nanjing.
Alsever ' s blood cell is preserved liquid: provided by Microbiological Lab of animal medicine institute of Agricultural University Of Nanjing.
The preparation of chicken erythrocyte suspension: gather chicken peripheral blood 5mL, transfer to 20mLAlsever ' s blood cell and preserve in liquid, 4 ℃ of preservations (holding time was no more than for 1 week).Before use, with normal saline washing 3 times, after each washing, with the centrifugal 5min of 2000r/min, regulating red cell suspension concentration with normal saline at last is 1%.
1.2 test method
1.2.1 animal grouping and processing
250 of the nonimmune healthy Luo Man egg cocks of 1 age in days are divided into high, medium and low dosage group, control drug group and blank group at random, and 50 every group, establish simultaneously 5 repetitions, each repeats 10.During 14 age in days with the weak malicious Seedling eye dripping collunarium of the new Zhi Erlian of 1 part.The blank group basal diet of feeding, drug component does not add the lentinan granule (in lentinan) of 50mg/kg (low dose group), 100mg/kg (middle dosage group), 200mg/kg (high dose group) level in basal diet, control drug group lentinan film is smashed Hou Jiashui to pieces and is gavaged 100mg/kg dosage, 24 ages in days are exempted from the weak malicious Seedling two of the newcastle IV of 1 part, and the new Zhi Erlian oil seepage of intramuscular injection simultaneously 0.3mL/ only.Whole 6 weeks of test period.
Respectively at after immunity the 7th, 14,21,28, every group of 35d and 42d randomly draw 10 chickens, venous blood collection under the wing, separation of serum, the HI method detects antibody titer.Simultaneously, after immunity 14,21,28, every group of 35d and 42d randomly draw 4 chickens and weigh, and cuts open and kill, and wins thymus, spleen and fabricius bursa and weigh, and calculates Immune Organs Index.
Empty stomach body weight (kilogram) before Immune Organs Index=immune organ fresh weight (gram)/government official
1.2.2 the chicken serum antibody titer of ND detects
The titration of 4 unit antigens is on 96 hole Microhemagglutination plates, and from left to right every sky adds PBS liquid 50 μ L, and another row is as repeating.The 1st hole to every row adds newcastle allantoic fluid 50 μ L again, successively backward doubling dilution until the 11st hole, the 12nd hole in contrast, without antigen liquid.Then add 1% chicken erythrocyte suspension 50 μ L to every hole, micro plate is shaken mixing and be placed in 37 ℃ of incubators sense and make 30min, observed result when the control wells erythrocyte has precipitated on micro oscillator.With the antigen maximum dilution hole of 100% coagulation as this antigen blood clotting valency, i.e. 1 coagulation unit; From this hole to the antigen diluent degree in reach 2 holes as the dilution factor of 4 unit antigens.
Sample detection adopts the antibody titer of hemagglutination inhibition test test sample, from left to right every hole adds PBS liquid 50 μ L on 96 hole Microhemagglutination plates, the 1st hole to every row adds serum 50 μ L to be checked again, successively backward doubling dilution until the 12nd hole, then add 4 unit antigen 50 μ L to every hole, the vibration mixing is placed on to feel in incubator and makes 20min on micro oscillator.Taking-up adds 1% chicken erythrocyte suspension 50 μ L to every hole, establish simultaneously positive serum, negative serum and blank hole.The vibration mixing is placed on to feel in 37 ℃ of incubators makes 30min, observed result when the control wells erythrocyte has precipitated.Suppress the serum greatest dilution of coagulation as the antibody titer of this serum take 100%, every group of meansigma methods with 8 chicken serum antibody titers represents the antibody horizontal of this group.
1.2.3 data analysis
Data with
Expression is carried out Duncan ' s multiple analysis with SPSS 16.0 softwares, and relatively antibody changes and organ index variation situation.
2 the results are shown in Table 1-7.
The affect comparative test result of the lentinan of table 1 embodiment 1 on chicken serum ND-HI antibody titer
The affect comparative test result of the lentinan of table 2 embodiment 1 on the Immune Organs of Chicken index
By data in table 1 as can be known, test proceeds to 7d and 14d, the horizontal there was no significant difference of ND-HI (P>0.05) between each group; After 14d, each test group of lentinan granule and control drug group ND-HI level all are significantly higher than blank group (P<0.05), lentinan granule high dose group ND-HI level is higher than control drug group (P<0.05), and middle dosage group ND-HI level is compared difference not remarkable (P>0.05) with the control drug group, and low dose group ND-HI level is significantly lower than control drug group (P<0.05).
By data in table 2 as can be known, each test group of lentinan granule and control drug group Immune Organs Index all are significantly higher than blank group (P<0.05), lentinan granule high dose group Immune Organs Index is higher than control drug group (P<0.05), and middle dosage group Immune Organs Index is compared difference not remarkable (P>0.05) with the control drug group, and the low dose group Immune Organs Index is significantly lower than control drug group (P<0.05).
The affect comparative test result of the lentinan of table 3 embodiment 2 on chicken serum ND-HI antibody titer
The affect comparative test result of the lentinan of table 4 embodiment 2 on the Immune Organs of Chicken index
By data in table 3 as can be known, test proceeds to 7d and 14d, the horizontal there was no significant difference of ND-HI (P>0.05) between each group; After 14d, each test group of lentinan granule and control drug group ND-HI level all are significantly higher than blank group (P<0.05), lentinan granule high dose group ND-HI level is higher than control drug group (P<0.05), and middle dosage group ND-HI level is compared difference not remarkable (P>0.05) with the control drug group, and low dose group ND-HI level is significantly lower than control drug group (P<0.05).By data in table 4 as can be known, each test group of lentinan granule and control drug group Immune Organs Index all are significantly higher than blank group (P<0.05), lentinan granule high dose group Immune Organs Index is higher than control drug group (P<0.05), and middle dosage group Immune Organs Index is compared difference not remarkable (P>0.05) with the control drug group, and the low dose group Immune Organs Index is significantly lower than control drug group (P<0.05).
The impact of the lentinan of the embodiment 3 of table 5 various dose on chicken serum ND-HI antibody titer
The impact of the lentinan of the embodiment 3 of table 6 various dose on the Immune Organs of Chicken index
By data in table 5 as can be known, test proceeds to 7d and 14d, the horizontal there was no significant difference of ND-HI (P>0.05) between each group; After 14d, each test group of lentinan granule and control drug group ND-HI level all are significantly higher than blank group (P<0.05), lentinan granule high dose group ND-HI level is higher than control drug group (P<0.05), and middle dosage group ND-HI level is compared difference not remarkable (P>0.05) with the control drug group, and low dose group ND-HI level is significantly lower than control drug group (P<0.05).By data in table 6 as can be known, each test group of lentinan granule and control drug group Immune Organs Index all are significantly higher than blank group (P<0.05), lentinan granule high dose group Immune Organs Index is higher than control drug group (P<0.05), and middle dosage group Immune Organs Index is compared difference not remarkable (P>0.05) with the control drug group, and the low dose group Immune Organs Index is significantly lower than control drug group (P<0.05).
The impact of the lentinan of the embodiment 4 of table 7 various dose on chicken serum ND-HI antibody titer
The impact of the lentinan of the embodiment 4 of table 8 various dose on the Immune Organs of Chicken index
By data in table 7 as can be known, test proceeds to 7d and 14d, the horizontal there was no significant difference of ND-HI (P>0.05) between each group; After 14d, each test group of lentinan granule and control drug group ND-HI level all are significantly higher than blank group (P<0.05), lentinan granule high dose group ND-HI level is higher than control drug group (P<0.05), and middle dosage group ND-HI level is compared difference not remarkable (P>0.05) with the medicine matched group, and low dose group ND-HI level is significantly lower than medicine matched group (P<0.05).By data in table 8 as can be known, each test group of lentinan granule and control drug group Immune Organs Index all are significantly higher than blank group (P<0.05), lentinan granule high dose group Immune Organs Index is higher than control drug group (P<0.05), and middle dosage group Immune Organs Index is compared difference not remarkable (P>0.05) with the control drug group, and the low dose group Immune Organs Index is significantly lower than control drug group (P<0.05).
Above-mentioned result of the test shows: the antibody titer of most of test group chickens and Immune Organs Index all are significantly higher than blank group (P<0.05), and present certain dose-effect relationship; This lentinan granule ND-HI antibody titer of Isodose and Immune Organs Index are a little more than the lentinan tablet.This result shows that the lentinan granule can significantly improve the ND-HI antibody titer level of chicken on the one hand, can promote the growth of bone-marrow-derived lymphocyte by affecting the growth of spleen, fabricius bursa on the other hand, thereby improve the body antibody horizontal.And lentinan granule convenient drug administration can reduce the stress that produces to the stimulation of animal body with due to administration, is convenient to it and applies on veterinary clinic.